Idiopathic pulmonary fibrosis (IPF) is a progressive fibroproliferative disorder with poor prognosis and generally ineffective therapy. A clearer understanding of the pathobiological processes leading to IPF has emerged over the last several years. This has led to efforts for generating targeted, novel, therapeutic approaches that translate these mechanistic observations from the bench to clinically relevant therapeutic trial. Three separate sentinel findings made at our institution have resulted in active therapeutic trials. These include: 1) an imbalance of leukotriene production in the lungs of IPF patients;2) inhibition of TGF-B production by the copper binding agent, tetrathyomolybdate (TM), ameliorates bleomycin induced fibrosis;and 3) the surgical lung biopsies and fibroblasts isolated from the lungs of IPF patients exhibit skewed cytokine transcript expression toward IL-13 and its receptors. We have designed three phase I or phase II clinical therapeutic trials based on these observations. These include: 1) a phase II randomized controlled trial of a 5-lipoxygenase inhibitor, zileuton, versus standard therapy with azathioprine and prednisone in IPF;2) a phase II safety/efficacy study of TM in advanced IPF;and 3) a phase I study assessing safety of a unique, IL-13-pseudomonas exotoxin chimeric molecule that targets fibroblasts in the lungs of IPF patients. The candidate for this award has extensive experience in patient-oriented research and has short and longterm goals of developing the expertise and creating the infrastructure required to form a critical nucleus of patient-oriented researchers that can optimally design and conduct clinically relevant therapeutic trials in this devastating disease. This process will create an optimal, comprehensive training environment for investigators that express an interest in patient-oriented research that carries forth molecular observations of disease pathogenesis into viable therapies. This will become particularly important if translational research is to keep pace as strides are made in the basic immunology, genetics and biochemistry of IPF.